Effects of phenylbutyrate on proliferation and apoptosis in human prostate cancer cells in vitro and in vivo

• Published in: International journal of oncology Vol. 14; no. 3; p. 501
• Main Authors: Melchior, S W, Brown, L G, Figg, W D, Quinn, J E, Santucci, R A, Brunner, J, Thüroff, J W, Lange, P H, Vessella, R L
• Format: Journal Article
• Language: English
• Published: Greece 01-03-1999
• Subjects: Androgens - pharmacology; Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Cycle - drug effects; Cell Differentiation - drug effects; Cell Division - drug effects; Disease Models, Animal; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Phenylbutyrates - pharmacology; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Transplantation, Heterologous; Tumor Cells, Cultured
• ISSN: 1019-6439
• DOI: 10.3892/ijo.14.3.501

Phenylbutyrate (PB) is a potent differentiating agent and currently under investigation for the treatment of prostate cancer (CaP) and other malignancies. We have studied the impact of PB in vitro and in vivo on differentiation, proliferation and apoptosis in the LNCaP and LuCaP 23.1 prostate cancer xenograft models. In vitro we found that i) PB increased PSA secretion/cell, ii) inhibited cell proliferation in a time- and dose-dependent manner resulting in a cell cycle arrest in G1-phase and iii) induced apoptosis at concentrations of 2.5 mM after 3 days of treatment. In PB treated animals tumor growth stabilized or regressed. Combination of castration and PB treatment had a synergistic antiproliferative effect. The growth-inhibitory and differentiating properties and a low toxicity profile of PB provide rationale for further clinical studies in patients with CaP.